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Is it all just a fluke? Lessons from Playing God in the Long-Term Evolution Experiment – by Brian Klaas

Our understanding of human history is a struggle between contingency and convergence. Do stable long-term trends drive change? Or does history revolve around the smallest details? We must speculate between the two worldviews because we cannot test the past experimentally.

But what if you could create multiple worlds? And what if you could not only control what happens inside, but also over time? Imagine the ability to play God, press pause whenever you want, and even rewind and replay key moments. That would give us a glimpse into the inner mysteries of cause and effect with unprecedented precision. We would finally know how change happens – and whether contingency or convergence prevails. It’s a heady thought experiment. But could it happen?

A few decades ago, a scientist named Richard Lenski realized this was possible without science fiction. Lenski, who sports an impressive Darwin-style beard, worked as an evolutionary biologist, conducting fieldwork in rural North Carolina to study the predatory southern ground beetle. He began to wonder whether experiments in evolutionary change could be conducted not in the untameable wilderness, but instead in the controlled environment of a scientific laboratory. In 1988, Lenski launched one of the longest-running and most important experiments in scientific history.

Lenski’s experiment is elegant in its simplicity. Take twelve identical flasks and fill them with twelve identical logs E.coli bacteria, give them exactly the same glucose broth and let them evolve further. Because E.coli reproduce rapidly, passing 6.64 generations per day. The average human generation lasts 26.9 years, so one day in the world of these bacteria is roughly equivalent to 178 years of human time. It’s hard to believe, but since 1988 Lenski has directly observed the evolution of more than 70,000 generations. E.coli, the human equivalent of 1.9 million years of change. In 2004, another notable scientist, Zachary Blount, joined Lenski’s laboratory. Together they have long overseen twelve microbial universes, each swirling around in a bottle.

I visited them so that I could also gaze into these controlled universes. Lenski and Blount’s lab at Michigan State University is unremarkable. There are beakers, graduated cylinders, petri dishes and white bottles of chemicals on packed shelves. Next to the door, Lenski points to a square incubator set at 37°C, the same temperature as the human body. The incubator hums as it slowly rotates and shakes a bottle of microbes.

Our understanding of human history is a struggle between contingency and convergence. Do stable long-term trends drive change? Or does history revolve around the smallest details?

Blount describes the experiment with enthusiasm. Every day, the bacteria in each of the flasks grow in an identical broth of glucose, or sugar, and citrate, better known as the “acid that gives orange juice its flavor.” The tiny organisms swim in citrate, but can only eat glucose. Instead of having sex to reproduce, bacteria divide into two nearly identical daughter cells. Variation in the cobs therefore usually results from mutations, or small errors in the DNA that occur during copying.

The genius of the experiment is that twelve different populations from one common ancestor are free to evolve under identical conditions. The experiment therefore eliminated sex, environmental changes and predators from the equation, allowing the scientists to observe evolution in its purest form.

Lenski and Blount can therefore test whether contingency or convergence rules hold. If change is driven by convergence, the twelve flasks should show only small variations even over long periods. They may take a dozen different paths, but they end up in roughly the same place. But if contingency dominates, the twelve populations should eventually diverge in substantial ways, as chance events create microbial freaks that change the path of evolution forever.

Lenski and Blount also have something that most scientists don’t: a time machine. E.coli can be frozen without damaging it, allowing freezers to act as a pause button. To press play, simply thaw the bacteria again. From the start, Lenski and his team froze all twelve bacterial lines every 500 generations, meaning they could repeat any part of the experiment from a given snapshot. Do you want to create a bacterial replay from the day the Soviet Union collapsed or from September 11, 2001? No problem. In those twelve broth universes, Lenski and Blount control time.

For more than a decade, the experiment seemed to support the evolutionary convergence hypothesis. The twelve cultures were different because small changes were inevitable. But all twelve seemed to change in largely similar ways. Each bacterial lineage gradually became better at eating glucose and became ‘fitter’ in the Darwinian sense. There was a clear sense of order. The specific mutations didn’t seem to make much difference. It was as if all twelve of them were following the same trail, all running toward the same destination.

For one line of bacteria, one small change meant everything about their future changed, all because of a random mutation made possible by four unrelated accidents.

Then, in January 2003, a postdoctoral researcher, Tim Cooper, arrived at the lab to care for the twelve populations, just as he had done hundreds of times before. This time something was different. Eleven populations looked normal, “like bottles of water with a few drops of milk mixed in, with only their slight cloudiness indicating the millions of bacteria present.” But the twelfth was very different. It was partially opaque, a cloudy mixture when it should have been mostly transparent and clear. “I thought it was a mistake,” Cooper told me. “But I was pretty sure there was something interesting going on.

Cooper called Lenski.

“I thought it was a lab error,” Lenski told me. “Our motto in the laboratory to prevent contamination is: when in doubt, throw it away.” Lenski decided to restart that bacterial line from the last frozen sample. Fortunately, mistakes were easily corrected with their microbial time machine. A few weeks later, the same bottle became cloudy again. Clearly there was no mistake. Something was going on.

Stunned, the scientists analyzed the DNA of the E.coli in that opaque bottle and found something incredible. The bacteria had developed the ability to eat the citrate they were swimming in, which should not have been possible. There was only one documented case of this in the twentieth century E.coli that could digest citrate. The fact that it had happened by chance was already an important discovery. But the story was about to get much more interesting.

To digest citrate, this ‘freak’ line of bacteria had first undergone at least four unrelated mutations that provided no clear benefit to the population – seemingly meaningless mistakes. But if these four mistakes had not all occurred in that specific order, the fifth mutation, which gave them the ability to eat citrate, would not have been possible. Five contingent mutations were stacked on top of each other, and they were also completely improbable. Contingency all the way down.

How contingent were they really? To find out, Blount spent years studying the freak population. He thawed samples of the mutant lineage at several points, using the frozen bacterial fossil record to test whether the ability to eat citrate would resurface. After analyzing about 40 trillion cells over nearly three years of experiments, he replicated the citrate mutation only seventeen times. But going back far enough in the bacterium’s evolutionary history, the citrate mutation never arose again. It was a contingency, through and through.

To us the world seems convergent, until we are shocked to realize that it is not.

To this day, only one in twelve generations, after 70,000 generations – equivalent to 1.9 million human life years of evolution – has developed the ability to digest citrate. For one line of bacteria, one small change meant everything about their future changed, all because of a random mutation made possible by four unrelated accidents. The other eleven bacterial universes are stuck eating glucose, blissfully unaware that they are swimming in, as Lenski puts it, a “lemony dessert.”

Blount argues that the Long-Term Evolution Experiment provides a sophisticated logic for thinking about crucial turning points in human society. For example, many historians say that D-Day was the key to the Allies’ victory in World War II. If you could test that claim experimentally, historians would follow the same research design as Lenski and Blount. Imagine having 1,000 identical Earths and being able to pause them at different times during the war. The logic would be that if Allied victory became much more likely with worlds starting after D-Day, historians might conclude that D-Day was the major turning point. But if the Allies won 75 percent of the time, regardless of whether the world thawed in June 1942 or June 1944, then it would be clear that the historians were wrong. D-Day didn’t matter much. It was always likely that the Allies would win.

Unfortunately, there is only one Earth, we cannot turn back time, and these contingency versus convergence experiments remain possible only with microbes in a science laboratory. At this point, however, it appears that Lenski and Blount – and a much larger team of researchers working on the Long-Term Evolution Experiment – ​​have settled the contingency versus convergence debate: to us, the world seems convergent, until we realize with a shock that that is not the case.


Today, the long-term evolution experiment continues under the leadership of Jeffrey Barrick of the University of Texas at Austin.

Derived from Fluke: Chance, chaos and why everything we do matters by Brian Klaas. Published by Scribner. Copyright © 2024 Brian Klaas. All rights reserved.